Is New Surveillance Monitoring Required for Enterococcal Oxazolidinone Resistance?

A new mechanism of oxazolidinone resistance in Enterococcus faecalis may warrant surveillance for further monitoring, according to a study recently published in the Journal of Antimicrobial Chemotherapy.

Although the oxazolidinone class of anti-gram-positive agents possesses potent activity against these isolates, resistance after prolonged administration can be acquired. Alterations in ribosomal oxazolidinone binding sites (23S rRNA; L3 and L4 proteins) are the most common resistance mechanisms, including a G2576T mutation on the 23S rRNA gene. Other transferable resistance determinants have been detected as newer mechanisms, including cfr, cfr(B), cfr(C), and optrA.

This study was conducted to evaluate the oxazolidinone resistance mechanisms of enterococci and further investigated the epidemiology and genetic context of optrA-carrying isolates.

Using the global collection of clinical isolates submitted between 2008 and 2016 to the SENTRY Antimicrobial Surveillance Program, enterococci exhibiting linezolid minimum inhibitory concentration (MIC) results of ≥4 mg/L were selected for further analysis.

A total of 36 E faecalis and 66 Enterococcus faecium isolates met the inclusion criteria, which constituted 0.38% of enterococci received between 2008 and 2016. E faecalis isolates had a linezolid MIC range of 4 to 16 mg/L, whereas E faecium isolates displayed slightly higher values, at 4 to 64 mg/L.

These isolates were subjected to the detection of cfr, cfr(B), cfr(C), and optrA mutations in the 23S rRNA-, L3, and L4-encoding genes by PCR, restriction digests, and sequencing.

Results showed distinct oxazolidinone-resistance mechanisms between E faecalis and E faecium. The sole oxazolidinone-resistance mechanism among E faecalis isolates from 2014 to 2016 was the presence of optrA (n=26), which was more prevalent than the presence of 23S rRNA alterations (n=9).

Of the E faecalis isolates, the optrA gene was found to be plasmid-located (n=22) and chromosome-located (n=3). The genetic context of optrA varied, and genetically distinct isolates from Ireland had an identical optrA context, indicating the potential for plasmid dissemination.

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Conversely, alterations in 23S rRNA remained the main oxazolidinone-resistance mechanism in E faecium, as all isolates contained G2576T alterations. Of these isolates, 3 (USA) had concomitant presence of cfr(B). The presence of cfr(B) was also reported in E faecalis for the first time. Among the optrA carrying E faecalis isolates, 3 (1 from Thailand; 2 from Panama) carried cfr and cfr(B), respectively.

The cfr or cfr(B) genes were always associated with another linezolid-resistance mechanism in E faecalis (optrA) and E faecium (G2576T), so it is unclear whether cfr confers linezolid resistance.

Although the majority of optrA genes were found in E faecalis, this gene has also been documented in other Gram-positive organisms and in in vitro transfer to different species. Therefore, the study authors conclude that, “it is important to monitor the emergence and spread of this resistance determinant at a local and regional level, especially due to the potential for E. faecalis to serve as a reservoir for spreading optrA to [multi-drug resistant] pathogens.”


Deshpande LM, Castanheira M, Flamm RK, Mendes RE. Evolving oxazolidinone resistance mechanisms in a worldwide collection of enterococcal clinical isolates: results from the SENTRY Antimicrobial Surveillance Program [published online June 6, 2018]. J Antimicrob Chemother. doi: 10.1093/jac/dky188